Early pregnancy peripheral blood gene expression and risk of preterm delivery: a nested case control study

<p>Abstract</p> <p>Background</p> <p>Preterm delivery (PTD) is a significant public health problem associated with greater risk of mortality and morbidity in infants and mothers. Pathophysiologic processes that may lead to PTD start early in pregnancy. We investigated early pregnancy peripheral blood global gene expression and PTD risk.</p> <p>Methods</p> <p>As part of a prospective study, ribonucleic acid was extracted from blood samples (collected at 16 weeks gestational age) from 14 women who had PTD (cases) and 16 women who delivered at term (controls). Gene expressions were measured using the GeneChip^®Human Genome U133 Plus 2.0 Array. Student's T-test and fold change analysis were used to identify differentially expressed genes. We used hierarchical clustering and principle components analysis to characterize signature gene expression patterns among cases and controls. Pathway and promoter sequence analyses were used to investigate functions and functional relationships as well as regulatory regions of differentially expressed genes.</p> <p>Results</p> <p>A total of 209 genes, including potential candidate genes (e.g. PTGDS, prostaglandin D2 synthase 21 kDa), were differentially expressed. A set of these genes achieved accurate pre-diagnostic separation of cases and controls. These genes participate in functions related to immune system and inflammation, organ development, metabolism (lipid, carbohydrate and amino acid) and cell signaling. Binding sites of putative transcription factors such as EGR1 (early growth response 1), TFAP2A (transcription factor AP2A), Sp1 (specificity protein 1) and Sp3 (specificity protein 3) were over represented in promoter regions of differentially expressed genes. Real-time PCR confirmed microarray expression measurements of selected genes.</p> <p>Conclusions</p> <p>PTD is associated with maternal early pregnancy peripheral blood gene expression changes. Maternal early pregnancy peripheral blood gene expression patterns may be useful for better understanding of PTD pathophysiology and PTD risk prediction.</p

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

Quantifying electronic band interactions in van der Waals materials using angle-resolved reflected-electron spectroscopy

High electron mobility is one of graphene's key properties, exploited for applications and fundamental research alike. Highest mobility values are found in heterostructures of graphene and hexagonal boron nitride, which consequently are widely used. However, surprisingly little is known about the interaction between the electronic states of these layered systems. Rather pragmatically, it is assumed that these do not couple significantly. Here we study the unoccupied band structure of graphite, boron nitride and their heterostructures using angle-resolved reflected-electron spectroscopy. We demonstrate that graphene and boron nitride bands do not interact over a wide energy range, despite their very similar dispersions. The method we use can be generally applied to study interactions in van der Waals systems, that is, artificial stacks of layered materials. With this we can quantitatively understand the 'chemistry of layers' by which novel materials are created via electronic coupling between the layers they are composed of.We are grateful to Marcel Hesselberth, Daan Boltje and Ruud van Egmond for technical assistance. We thank Charles Kane for fruitful discussions and Kenji Watanabe for supplying the hBN base crystal. This work was supported by the Spanish Ministry of Economy and Competitiveness MINECO (project number FIS2013-48286-C2-1-P) and the Netherlands Organization for Scientific Research (NWO) via an NWO-Groot grant ('ESCHER'), a VIDI grant (680-47-502, S.J. v.d.M.), a VENI grant (680-47-447, J.J.) and by the FOM foundation via the 'Physics in 1D' programme. C.R.D. acknowledges support from NSF grant DMR-1463465

Reference values for generic instruments used in routine outcome monitoring: the leiden routine outcome monitoring study

<p>Abstract</p> <p>Introduction</p> <p>The Brief Symptom Inventory (BSI), Mood & Anxiety Symptom Questionnaire −30 (MASQ-D30), Short Form Health Survey 36 (SF-36), and Dimensional Assessment of Personality Pathology-Short Form (DAPP-SF) are generic instruments that can be used in Routine Outcome Monitoring (ROM) of patients with common mental disorders. We aimed to generate reference values usually encountered in 'healthy' and ‘psychiatrically ill’ populations to facilitate correct interpretation of ROM results.</p> <p>Methods</p> <p>We included the following specific reference populations: 1294 subjects from the general population (ROM reference group) recruited through general practitioners, and 5269 psychiatric outpatients diagnosed with mood, anxiety, or somatoform (MAS) disorders (ROM patient group). The outermost 5% of observations were used to define limits for one-sided reference intervals (95^th percentiles for BSI, MASQ-D30 and DAPP-SF, and 5^th percentiles for SF-36 subscales). Internal consistency and Receiver Operating Characteristics (ROC) analyses were performed.</p> <p>Results</p> <p>Mean age for the ROM reference group was 40.3 years (SD=12.6) and 37.7 years (SD=12.0) for the ROM patient group. The proportion of females was 62.8% and 64.6%, respectively. The mean for cut-off values of healthy individuals was 0.82 for the BSI subscales, 23 for the three MASQ-D30 subscales, 45 for the SF-36 subscales, and 3.1 for the DAPP-SF subscales. Discriminative power of the BSI, MASQ-D30 and SF-36 was good, but it was poor for the DAPP-SF. For all instruments, the internal consistency of the subscales ranged from adequate to excellent.</p> <p>Discussion and conclusion</p> <p>Reference values for the clinical interpretation were provided for the BSI, MASQ-D30, SF-36, and DAPP-SF. Clinical information aided by ROM data may represent the best means to appraise the clinical state of psychiatric outpatients.</p